Middendorf TR , Aldrich RW , Baylor DA .

EY01543 NEI NIH HHS , NS23294 NINDS NIH HHS

	Figure 1. Schematic for photochemical modification of tryptophan. At room temperature, tryptophan molecules occupy the electronic ground state almost exclusively (bottom left). Absorption of a UV photon promotes tryptophan to an excited electronic state (*). The lifetime of the excited state is several nanoseconds (Beechem and Brand 1985). The excited tryptophan may decay back to the ground state by a number of paths; the sum of the rate constants for these deactivation pathways is denoted kd. Alternatively, the reactive excited molecule may form a covalently modified product by deactivating along one of the photochemical reaction pathways indicated by the rate constants k1 through k5. The major products of the UV photolysis of free tryptophan in aqueous solution include kynurenine, serine, tryptamine, aspartic acid, and N-formyl kynurenine (Creed 1984a). The photochemical reactivity depicted here is a general property of organic molecules. We exploited this reactivity by using UV light to “mutagenize” functional ion channel proteins in situ while observing simultaneously the effect on macroscopic ionic currents through the channels.
	Figure 2. Removal of scattering and contaminant artifacts from tryptophan and tyrosine absorption spectra. (A) Absorption spectrum of tryptophan in standard sodium solution at pH 7.6. The solid trace is the spectrum of 312 μM tryptophan from 225 to 310 nm spliced onto that of 27 mM tryptophan from 310 to 400 nm. The extinction coefficient (M−1 · cm−1) was computed from the absorbance using Beer's law (), and is plotted as a function of wavelength in nanometers on semi-logarithmic coordinates. Also shown is the fluorescence excitation spectrum of 42 mM tryptophan from 320 to 340 nm (•) scaled to match the absorption spectrum at 320 nm. The emission wavelength for the fluorescence excitation spectrum was 360 nm. (B) Absorption spectra of tyrosine and related compounds in aqueous solution. The extinction coefficients of tyrosine (143 μM, thin line) and the dipeptide Tyr-Ala (129 μM, bold line) in standard sodium solution, pH 7.6, are plotted as a function of wavelength on semi-logarithmic axes. Also shown is the spectrum of Tyr-Ala (129 μM, dashed line) in the same solvent at pH 5.6. The Tyr-Ala spectra were scaled to the same amplitude as the tyrosine spectrum at 275.6 nm to facilitate comparison.
	Figure 3. Absorption spectra of near-UV absorbing amino acids. Extinction coefficients (M−1 · cm−1) were computed from absorbance values using Beer's law (), and are plotted against wavelength on semi-logarithmic coordinates. The compounds, symbols, wavelengths of maximal near-UV absorption, λmax, and extinction coefficients at λmax are: tryptophan (solid bold line), 279.7 nm and 5,659; tyrosine (in the form of the dipeptide Tyr-Ala, pH 7.6, see materials and methods) (dashed bold line), 275.6 nm and 1,330; phenylalanine (dot-and-dashed line), 257.7 nm and 187, tyrosinate (ionized tyrosine formed by dissolving tyrosine in 100 mM NaOH) (short dashed line), 293.5 nm and 2,240; the thiolate form of cysteine (ionized cysteine formed by dissolving cysteine in 100 mM NaOH) (long dashed line), 237.1 nm and 7,146; and cystine (thin solid line), 247 nm and 465. All compounds except tyrosinate and the thiolate anion of cysteine were dissolved in the standard sodium solution described in materials and methods. Histidine, which also contains an extended pi electron system, does not absorb significantly at these wavelengths.
	Figure 4. Characterization of UV-activated conductance in Xenopus oocytes. (A) UV effect on the current through an excised, inside-out patch from an uninjected oocyte in response to a 0–50-mV voltage step. UV doses (in photons × 108 · μm−2) are indicated. The patch was irradiated in the absence of cGMP while held at 0 mV. (B) Voltage dependence of UV-activated conductance. Results for patch from A after exposure to 5.41 × 1010 photons · μm−2. Currents were elicited by stepping the patch from a holding potential of 0 mV to voltages from −80 to +70 mV in 10-mV increments. (C) Current–voltage relation (•) for the results in B. The fit is a straight line with slope 4.6 × 10−8 S. (D) Cation selectivity of UV-activated conductance. Currents were elicited by voltage ramps from −75 to +75 mV in 500 ms after exposing the patch to 1.78 × 1010 photons · μm−2. The trace indicated by * was obtained in symmetric 130-mM NaCl solutions; the other trace was obtained with 130 mM NaCl in the pipet and 26 mM NaCl in the bath. Voltages were not corrected for junction potentials. The results are from a different patch than that used in A–C. The currents in A–D were corrected for leak through the seal resistance by subtracting the current before irradiation.
	Figure 5. Dose dependence of UV-activated conductance. (A) UV dose–response relations for UV-activated conductances from nine patches. The total patch current in picoamperes is plotted as a function of the cumulative photon dose. Different symbols indicate separate experiments. Patches were irradiated while held at 0 mV and currents were recorded at +50 mV. The bath and pipet contained standard sodium solution with no cGMP (see materials and methods). (B) Results from A, plotted on double logarithmic coordinates. (C) Same as B, except the results from each experiment were shifted along the ordinate to correct for the difference in current amplitudes at 3 × 1010 photons · μm−2. The solid line is a fit to the combined results using the modified all-or-none model () with the target number n* equal to 4.3 ± 0.5. Currents in A–D were corrected for leak through the seal resistance by subtracting the current before irradiation.
	Figure 6. Effect of UV light on CNG channel currents. (A) Ionic currents before and after UV exposure. The currents were recorded in symmetrical 130-mM NaCl from an excised, inside-out membrane patch from a Xenopus oocyte membrane expressing bovine rod CNG (RET) channels. The template at top shows the timing of the voltage step. The bold trace at top is the current in the presence of 100 μM (approximately half-saturating) intracellular cGMP before UV exposure. The solid traces of successively smaller amplitude were obtained after increasing cumulative UV exposures. UV doses (in photons × 108 · μm−2) are indicated for selected traces. The patch was irradiated with light from a xenon arc lamp (280 nm) in the absence of cGMP. The light intensity was 4.6 × 108 photons μm−2 s−1. The cyclic GMP-activated currents were corrected for leak by subtracting the current in the absence of cGMP after the same dose. The dashed trace shows the leak current before irradiation. The initial cGMP-activated current was 1,120 pA; the current at the end of the experiment (after a cumulative dose of 1.3 × 1010 photons · μm−2) was 125 pA. (B) Light and time dependence of currents. The channel current (I), normalized by the current before UV exposure (I0), is plotted as a function of time during the experiment. Each open symbol represents the current recorded after a 1-s exposure containing 4.6 × 108 photons · μm−2 except for the last two open symbols, which were recorded after 5-s exposures that each contained 2.3 × 109 photons · μm−2. Closed symbols denote currents recorded with no intervening UV exposure. Arrows indicate timing of UV applications. Results are from patch in A.
	Figure 7. Evidence that the UV effect involves a one-photon absorption mechanism. (A and B) UV dose dependence of currents through RET channels. Patches were irradiated with a low-intensity continuous xenon arc lamp (λ = 280 nm, six patches, A) or a high-intensity pulsed UV laser (λ = 266 nm, six patches, B). Different symbols indicate separate experiments. To facilitate comparison of the shapes of the curves, results from each experiment were shifted along the abscissa so that the D1/2 value was equal to its average value for the unshifted results for all experiments at similar light intensities. The D1/2 values for the unshifted results ranged from 3.18 to 5.23 × 109 photons · μm−2, with an average of (3.84 ± 0.39) × 109 photons · μm−2 (mean ± SEM) for low-intensity excitation, and from 3.2 to 8.4 × 109 photons · μm−2, with a mean of (4.68 ± 0.78) × 109 photons · μm−2 for high-intensity excitation. The smooth curve in each panel is a fit to the collected results using of the text. The fitting parameter n*, which provides a measure of the maximum steepness of the relation, was equal to 1.21 ± 0.05 (mean ± SD) and 1.33 ± 0.03, respectively, for the results in A and B. Currents in A were recorded in 100 μM cGMP after irradiating the patches in the absence of cGMP. Currents in B were measured in 100 μM cGMP after irradiating the patches in the presence of 100 μM cGMP. The arc lamp intensities ranged (0.32–1.5) × 108 photons · μm−2 · s−1 for different experiments; the laser intensities ranged (2.1–3.9) × 1016 photons · μm−2 · s−1, and were corrected for attenuation by cGMP in the bath solution. (C) Comparison of the UV effect at low- and high-light intensities with predictions for one- and two-photon absorption mechanisms. The ordinate is the ratio of τlo to τhi, where τlo and τhi are the average UV exposure times required to reduce the current to half of its maximal (pre-UV) amplitude following low- or high-intensity irradiation, respectively. The ratio τlo /τhi computed from the results in A and B was 2.32 × 108. The theoretical ratios were calculated using and were 1.09 × 108 and 1.20 × 1016 for one- and two-photon absorption mechanisms, respectively. The slight difference in UV wavelengths used in A (280 nm) and B (266 nm) has a minimal effect (<7%) on the channels' UV sensitivity (see Fig. 9).
	Figure 8. UV dose–response relations of RET channels irradiated at different wavelengths. (A) The channel current amplitude in saturating (1 mM) cGMP, I, normalized by the pre-UV amplitude, I0, is plotted as a function of UV dose on semilogarithmic coordinates. Each type of symbol represents collected results from 3–10 separate patches at a given wavelength. The UV dose that reduced the current to half of its initial value, D1/2, was estimated from fits to the results for each experiment using . To facilitate comparison of the shapes of the relations, the results from each experiment were shifted along the abscissa so that D1/2 was equal to the average D1/2 of the unshifted results for all experiments at the same wavelength. Smooth curves are fits to the collected results at each wavelength using . The excitation wavelengths, symbols, and number of experiments were: 250 nm (•), 3; 270 nm (□), 4; 290 nm (⋄), 3; 310 nm (▴), 3; and 330 nm (▿), 2. The light source was a xenon arc lamp; light intensities ranged from 1.3 × 107 to 2.7 × 109 photons · μm−2 · s−1. Currents through channels activated by 1 mM (saturating) cGMP were recorded at +50 mV. Cyclic GMP was absent during irradiation. (B) Same as A, except the wavelengths, symbols, and number of experiments were: 260 nm (▪), 3; 280 nm (○), 10; 300 nm (▵), 4; and 320 nm (♦), 4.
	Figure 9. Wavelength dependence of UV sensitivity of CNG channels. (A) Action spectrum of UV effect compared with wavelength dependence of tryptophan and tyrosine absorption. The UV sensitivity at each excitation wavelength λ, defined as the reciprocal of D1/2(λ), was obtained from the fits in Fig. 8. Also shown is the UV sensitivity at 266 nm, obtained from the results in Fig. 7 B. The UV sensitivity (•, mean ± SEM), normalized to a value of 1.0 at 270 nm, is plotted as a function of wavelength on semilogarithmic coordinates. The predicted action spectra for photochemical modification of tryptophan (solid line) and tyrosine (dotted line) targets were calculated from their absorption spectra (Fig. 3) using and were normalized to a value of 1 at 270 nm. (B) Wavelength dependence of slope factor. The slope factors from the fits to the results in Fig. 7 B and 8 are plotted as a function of wavelength on linear coordinates. The experimental points (•) are mean ± SD. Dashed lines show the range of the estimated slope factors for excitation wavelengths between 260 and 310 nm.
	Figure 10. Environmental effects on tryptophan absorption. (A) Absorption spectra of tryptophan (trp) in aqueous buffer, and the tryptophan derivative NATrpA in various organic solvents. The compounds/solvents, symbols, solvent abbreviations, wavelengths of maximal absorption, and spectral widths (FWHM in nanometers) were: trp/water (solid bold line, H2O, 279.7 nm, 37.7); NATrpA/acetonitrile (thin dashed line, ACN, 281.0 nm, 35.9); NATrpA/methanol (bold dashed line, MeOH, 280.7 nm, 35.7); NATrpA/ethanol (thin solid line, EtOH, 282.3 nm, 35.4); NATrpA/N,N dimethylformamide (dot-and-dashed line, DMF, 283.1 nm, 35.0); and NATrpA/dimethylsulfoxide (long dashed line, DMSO, 283.8 nm, 35.1). Extinction coefficients (M−1 · cm−1) are plotted as a function of wavelength on linear coordinates. The spectra in organic solvents are scaled to the same maximal extinction coefficient as that of tryptophan in buffer to facilitate comparison. (B) Comparison of tryptophan absorption in different solvents to CNG channel action spectrum. The right-hand ordinate shows the ratio of the tryptophan absorption probability at 280 and 300 nm, A280/A300. The absorption ratios were computed from the spectra in A using . The ratios were: Trp/H2O, 15.7; NATrpA/ACN, 13.9; NATrpA/MeOH, 14.01; NATrpA/EtOH, 12.5; NATrpA/DMF, 5.8; and NATrpA/DMSO, 4.3. The UV sensitivity ratio of RET channels at these same wavelengths (S280/S300, left-hand ordinate) was 17.1 ± 2.0 (Fig. 8 and Fig. 9).
	Figure 11. UV modification of free tryptophan in aqueous solution. (A) Effect of UV irradiation on the absorption spectrum of tryptophan. Absorption spectra of 25 μM tryptophan in standard sodium solution (see materials and methods), pH 7.6, before UV and after exposure to 3.13 × 1010 photons · μm−2 at 280 nm. (B) Dose dependence of UV modification of free tryptophan. Photochemical modification of tryptophan by 280 nm UV was followed by monitoring the absorbance changes at 280 nm (•) and 310 nm (▪). The absorbance change at each wavelength [ΔA(D)] normalized to the maximal absorbance change at the same wavelength [ΔA(∞)] is plotted as a function of the photon dose. Smooth curves are fits to the absorbance changes using . Half-maximal UV doses (D1/2) and total photochemical quantum yields (Σφi, see ) were 57.8 × 108 photons · μm−2 and 0.055 ± 0.005, respectively, at 280 nm and 122.8 × 108 photons · μm−2 and 0.026 ± 0.001, respectively, at 310 nm.
	Figure 12. UV sensitivity of CNG channel tryptophan mutants. (A) Schematic diagram of RET channel α subunit indicating the positions and presumed locations of the 10 tryptophan residues in each subunit of the bovine retinal cGMP-gated channel. (B) UV dose–response relations of RET channel tryptophan point mutants. Each type of symbol represents collected results for one mutant. Mutations, D1/2 values in photons · 108 · μm−2, and the corresponding symbols are: W9F, 43.9 (○); W166F, 47.7 (□); W178F, 24.1 (▵); W198F, 37.4 (▿); W263I, 35.1 (wide diamond); W311F, 32.6 (tall diamond); W330F, 52.8 (⋄); W353Y, 6.7 (•); W435F, 43.3 (▹◃); and W440Y, 47.8 (hourglass). The dashed curve is a fit to the results for W353Y channels using ; the solid curve is a fit of this model to the collected results for all other mutants. Channels were irradiated in the absence of ligand at 280 nm. (C) Comparison of UV sensitivities of wild-type and tryptophan mutant channels. UV sensitivities, relative to the value for wild-type (WT) RET channels, are shown on the ordinate for each tryptophan point mutant.
	Figure 13. Modeling of UV dose–response relation. (A) Independent, all-or-none model. UV dose–response relation of CNG channels irradiated with 280 nm UV. Open symbols represent results for wild-type RET channels; solid symbols are for W353Y mutant channels. Channels were irradiated in the absence of ligand. Smooth curves are fits of the independent, all-or-none model () to the collected results for each type of channel. The critical target number (n*) was set to one (narrow dotted line), two (dotted line), three (long dotted line), or four (dashed line) for wild-type channels. Also shown is the best fit (solid line) to the UV dose–response relation of RET W353Y channels for n = 2 and n* = 1. A total of two targets per channel subunit was assumed in the fits; however, this parameter had little effect on the quality of the fits, which was determined mainly by the slope factor n*. (B) Proportional conductance model. Smooth curves are fits of the proportional conductance model () to the same results as shown in A. The simulated curves were independent of the total target number n. The best fit to the results for wild-type channels (solid line) was obtained for φ = 0.072. Simulated curve for W353Y was identical to the curve for wild-type channels if the same quantum yield was assumed. (C) Energy additive model. Smooth curves are fits of the energy additive model () to the same results as shown in A assuming one to four targets per subunit for wild-type channels and using a free energy difference ΔG0(0) of −3.0 RT. Also shown is a fit to UV dose–response relation of W353Y channels (solid line) with the quantum yield for target modification fixed to the same value as that of wild-type channels and assuming three targets per subunit and ΔG0(0) = +4.0 RT. Fitting parameters for all three models are summarized in Table .
	Figure 14. Effect of UV light on currents carried by different monovalent cations. (A–F) RET channel currents in the presence of 500 μM cGMP before UV (*) and after exposing patch to a dose of 5.07 × 109 photons · μm−2 from a high-intensity pulsed UV laser (λ = 266 nm). The pipet contained 130 mM NaCl for all experiments, and the bath solution contained 130 mM of LiCl (A); NaCl (B); KCl (C); NH4Cl (D); RbCl (E); or CsCl (F). Reversal potentials (mV) before and after irradiation were: (A) 12.6 and 8.6; (B) 0 and 0; (C) 1.1 and −0.1; (D) −27.4 and −25.7; (E) 17.0 and 10.0; and (F) 28.4 and 22.3. The voltages were not corrected for junction potentials. The patch was irradiated in the presence of 100 μM cGMP. The voltage was ramped between −50 and + 50 mV in 600 ms. The laser intensity was 1.49 × 1016 photons · μm−2 · s−1.
	Figure 15. (A) Effect of UV light on relative monovalent cation permeabilities of RET channels. The permeability ratios of various monovalent cations (X+ = Li+, Na+, K+, NH4+, Rb+, and Cs+) relative to that of Na+ are plotted before (•) and after (○) UV irradiation of the channels. Permeability ratios were calculated from the Goldman-Hodgkin-Katz equation () using the reversal potentials obtained from the results in Fig. 14. (B) UV effect on RET channel currents carried by different monovalent cations. The ordinate shows the outward current amplitude after UV irradiation, I(D), divided by that before UV, I(0), for the results in Fig. 14.
	Figure 16. Contribution of cystine photolysis to UV effect on CNG channels. Symbols show the action spectrum of the UV effect on RET channels (mean ± SEM, •, results from Fig. 9 A). Also shown is a fit to the action spectrum (bold line) using a linear combination of the filter-corrected absorption spectra (see materials and methods and Fig. 3) of tryptophan (thin line) and cystine (dashed line) in aqueous buffer. Relative contributions of the spectral components were 1.0 for tryptophan and 0.93 for cystine.

AUGENSTINE, The inactivation of trypsin by ultraviolet light. I. The correlation of inactivation with the disruption of constituent cystine. 1961, Pubmed

AUGENSTINE, The inactivation of trypsin by ultraviolet light. I. The correlation of inactivation with the disruption of constituent cystine. 1961, Pubmed
Akabas, Acetylcholine receptor channel structure probed in cysteine-substitution mutants. 1992, Pubmed , Xenbase
Altenhofen, Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium. 1991, Pubmed , Xenbase
BOOTH, The photochemical action of ultra-violet light on isolated single nerve fibres. 1950, Pubmed
Becchetti, Cyclic nucleotide-gated channels. Pore topology studied through the accessibility of reporter cysteines. 1999, Pubmed , Xenbase
Beechem, Time-resolved fluorescence of proteins. 1985, Pubmed
Bishop, Photodestruction of acetylcholinesterase. 1980, Pubmed
Brown, Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels. 1998, Pubmed , Xenbase
Bucossi, Single-channel properties of ionic channels gated by cyclic nucleotides. 1997, Pubmed , Xenbase
Busath, Ultraviolet flash photolysis of gramicidin-doped lipid bilayers. 1988, Pubmed
Chothia, Structural invariants in protein folding. 1975, Pubmed
Cooper, The effect of ultraviolet irradiation on soluble collagen. 1965, Pubmed
Dhallan, Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. 1990, Pubmed
Fesenko, Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. , Pubmed
Fodor, Mechanism of tetracaine block of cyclic nucleotide-gated channels. 1997, Pubmed , Xenbase
Fodor, Tetracaine reports a conformational change in the pore of cyclic nucleotide-gated channels. 1997, Pubmed , Xenbase
Fox, Modification of ionic membrane currents of Ranvier nodes by UV-radiation under voltage clamp conditions. 1971, Pubmed
Fujimori, Ultraviolet light irradiated collagen macromolecules. 1966, Pubmed
Gordon, "Light" reading: targeting tryptophans in cyclic nucleotide-gated channels. 2000, Pubmed
Gordon, Localization of regions affecting an allosteric transition in cyclic nucleotide-activated channels. 1995, Pubmed , Xenbase
Gordon, Direct interaction between amino- and carboxyl-terminal domains of cyclic nucleotide-gated channels. 1997, Pubmed
Gordon, A histidine residue associated with the gate of the cyclic nucleotide-activated channels in rod photoreceptors. 1995, Pubmed , Xenbase
Gordon, Altered ligand specificity by protonation in the ligand binding domain of cyclic nucleotide-gated channels. 1996, Pubmed , Xenbase
Goulding, Molecular mechanism of cyclic-nucleotide-gated channel activation. 1994, Pubmed , Xenbase
Goulding, Molecular cloning and single-channel properties of the cyclic nucleotide-gated channel from catfish olfactory neurons. 1992, Pubmed
Grossweiner, Photochemical inactivation of enzymes. 1976, Pubmed
Haynes, Single cyclic GMP-activated channel activity in excised patches of rod outer segment membrane. , Pubmed
Hibbard, The effect of pH on the aerobic and anaerobic photolysis of tryptophan and some tryptophan-containing dipeptides. 1985, Pubmed
Hsu, Ultra-violet light-induced changes in membrane properties in secretory cells. 1999, Pubmed
IMAHORI, The ultraviolet inactivation of pepsin. 1955, Pubmed
Jones, Tryptophan photolysis is responsible for gramicidin-channel inactivation by ultraviolet light. 1986, Pubmed
Kaupp, Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. 1989, Pubmed , Xenbase
Kramer, Antagonists of cyclic nucleotide-gated channels and molecular mapping of their site of action. 1996, Pubmed
Kunz, Photodynamic and radiolytic inactivation of ion channels formed by gramicidin A: oxidation and fragmentation. 1995, Pubmed
Lieberman, Ultraviolet radiation effects on isolated nerve fibers. 1970, Pubmed
Liu, Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. 1994, Pubmed
Liu, Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function. 1996, Pubmed
Liu, Constraining ligand-binding site stoichiometry suggests that a cyclic nucleotide-gated channel is composed of two functional dimers. 1998, Pubmed
Ludwig, Primary structure of cAMP-gated channel from bovine olfactory epithelium. 1990, Pubmed
Lynch, Nitric oxide inhibition of the rat olfactory cyclic nucleotide-gated cation channel. 1998, Pubmed
MCLAREN, Mechanism of inactivation of enzyme proteins by ultraviolet light. 1961, Pubmed
MONOD, ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. 1965, Pubmed
Maiti, Measuring serotonin distribution in live cells with three-photon excitation. 1997, Pubmed
Matthews, Ultraviolet difference spectra of the lactose repressor protein. 1973, Pubmed
McKim, Direct observation of differential UV photolytic degradation among the tryptophan residues of gramicidin A in sodium dodecyl sulfate micelles. 1993, Pubmed
Mendez, Near-visible ultraviolet light induces a novel ubiquitous calcium-permeable cation current in mammalian cell lines. 1998, Pubmed
Middendorf, Effects of ultraviolet modification on the gating energetics of cyclic nucleotide-gated channels. 2000, Pubmed , Xenbase
Miller, Interior and surface of monomeric proteins. 1987, Pubmed
Morrill, Isolation of a single carboxyl-carboxylate proton binding site in the pore of a cyclic nucleotide-gated channel. 1999, Pubmed , Xenbase
Nakamura, A cyclic nucleotide-gated conductance in olfactory receptor cilia. , Pubmed
Noren, A general method for site-specific incorporation of unnatural amino acids into proteins. 1989, Pubmed
Nowak, In vivo incorporation of unnatural amino acids into ion channels in Xenopus oocyte expression system. 1998, Pubmed , Xenbase
Nozaki, The solubility of amino acids and two glycine peptides in aqueous ethanol and dioxane solutions. Establishment of a hydrophobicity scale. 1971, Pubmed
Oxford, Ultraviolet photoalteration of ion channels in voltage-clamped lobster giant axons. 1975, Pubmed
Paoletti, C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating. 1999, Pubmed
Peters, A microfluorimetric study of translational diffusion in erythrocyte membranes. 1974, Pubmed
Richards, The interpretation of protein structures: total volume, group volume distributions and packing density. 1974, Pubmed
SETLOW, The action of monochromatic ultraviolet light on proteins. 1957, Pubmed
SETLOW, The effect of temperature on the ultraviolet light inactivation of trypsin. 1954, Pubmed
Saks, An engineered Tetrahymena tRNAGln for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression. 1996, Pubmed , Xenbase
Stühmer, Photobleaching through glass micropipettes: sodium channels without lateral mobility in the sarcolemma of frog skeletal muscle. 1982, Pubmed
Sun, Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating. 1996, Pubmed
Tallmadge, The rates of photolysis of the four individual tryptophan residues in UV exposed calf gamma-II crystallin. 1990, Pubmed
Tibbs, Allosteric activation and tuning of ligand efficacy in cyclic-nucleotide-gated channels. 1997, Pubmed , Xenbase
Varnum, Interdomain interactions underlying activation of cyclic nucleotide-gated channels. 1997, Pubmed , Xenbase
Varnum, Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels. 1995, Pubmed
Vladimirov, Photochemical reactions in amino acid residues and inactivation of enzymes during U.V.-irradiation. A review. 1970, Pubmed
WEBER, Fluorescence-polarization spectrum and electronic-energy transfer in tyrosine, tryptophan and related compounds. 1960, Pubmed
Walrant, N-formyl-kynurenine, a tryptophan photooxidation product, as a photodynamic sensitizer. 1974, Pubmed
Wang, An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. 1999, Pubmed
Yau, Cyclic GMP-activated conductance of retinal photoreceptor cells. 1989, Pubmed
Zimmerman, Cyclic GMP-sensitive conductance of retinal rods consists of aqueous pores. , Pubmed
Zimmerman, Hindered diffusion in excised membrane patches from retinal rod outer segments. 1988, Pubmed
Zong, Three amino acids in the C-linker are major determinants of gating in cyclic nucleotide-gated channels. 1998, Pubmed